The present invention relates to the prophylactic and therapeutic treatment of hypoxia and ischemic tissue disease. Phosphonate compounds are administered therapeutically to protect a tissue or organ against degeneration, necrosis and fibrosis following blockage of the blood supply to that tissue or organ. In the alternative, phosphonate compounds are administered prophylactically for the prevention of tissue or organ necrosis caused by ischemia of that tissue or organ, whatever the primary cause or etiology.
Hypoxia is a term to connote an inadequate supply of oxygen available to, or utilized by, tissue, without regard to cause or degree. Hypoxia can be the result of disease states, as in the case of the various anemias, or can result from a low oxygen tension in the blood, as in the case of high altitude "sickness".
Ischemia is a term used to connote, in an overall way, localized tissue anemia due to the obstruction of the flow of arterial blood or to vasconstriction. Obstruction or stenosis of a blood vessel to a tissue or organ results in tissue damage, progressive degeneration, and ultimate necrosis and fibrosis of that tissue or organ.
Ischemia can be the result of either the precipitous stoppage of arterial blood flow, or the more gradual, but usually progressive, diminution of flow. For example, ischemic heart disease can be caused by coronary occlusion (myocardial infarction) or by a more generalized coronary artery insufficiency. Cerebral ischemias and other tissue ischemias such as renal and bone infarcts are well-recognized disease states which are difficult to treat. Another disease state of this general type involves the ischemia of the peripheral tissues secondary to diabetes mellitus, and it is this type of ischemic disease which can result in retinopathies, loss of renal function, neuropathies, or necrosis and amputation of limbs in extreme cases.
By the present invention, certain phosphonate compounds, especially diphosphonates, are used in the treatment of hypoxia and ischemic tissue diseases. Such diseases include: myocardial infarction; senility; microangiopathies, including retinopathy, neuropathy, and chronic renal failure; pernicious anemia; iron-deficiency anemia; allergic reactions such as immediate and delayed hypersensitivity; and chronic hypoxic lung diseases such as emphysema, asthma, hyaline-membrane disorders, chronic bronchitis and cor pulmonale.